CN102516122A - Environment friendly method for preparing DMF (Dimethyl Formamide) solution of 2-hydroxy-benzonitril, DMF solution of 2-hydroxy-benzonitril and application thereof - Google Patents
Environment friendly method for preparing DMF (Dimethyl Formamide) solution of 2-hydroxy-benzonitril, DMF solution of 2-hydroxy-benzonitril and application thereof Download PDFInfo
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Abstract
The invention discloses an environment friendly method for preparing a DMF (Dimethyl Formamide) solution of 2-hydroxy-benzonitril, which is characterized in that triphosgene and salicylamide are respectively added into DMF to be fully reacted. With the preparation method disclosed by the invention, more than 98% of 2-hydroxy-benzonitril (excluding solvent) can be obtained, the chemical conversion and the selectivity are both greater than 98%, and no problems exist if the 2-hydroxy-benzonitril is directly applied for the next step of reaction. In the process of production, no polluting waste gas and waste water are discharged, scraps are inorganic salts which can directly used or organic amine hydrochlorides which can be recycled, the comprehensive production cost of the 2-hydroxy-benzonitril is greatly reduced, and the production process is environment friendly.
Description
Technical field
This discovery relates to a kind of method of DMF solution of eco-friendly preparation salicylonitrile, the DMF solution and the application thereof of salicylonitrile.
Background technology
Salicylonitrile, the popular name salicylonitrile has another name called 2-hydroxy-phenylformonitrile, o-hydroxy nitrile, 2-cyanophenol etc., molecular formula C7H5NO, CAS registration number 611-20-1, have necessarily water-soluble, Pka=7.17, unstable to highly basic and oxygenant.Can synthesize treatment hypertension and angina drug Betriol (Boehringer,Ing.) as medicine intermediate, as pesticide intermediate, can the synthesizing fungicide ICIA 5504, can also synthesize multiple spices and liquid crystal material etc. in addition.
Salicylic amide, the red crystalline powder of white or micro mist.140 ℃ of fusing points.Salicylic amide is soluble in hot water, alcohol, ether and chloroform, is slightly soluble in cold water.The pH of 28 ℃ of saturated aqueous solutions is about 5.Salicylic amide is bitter taste slightly.Antipyretic and analgesic also is used to produce O-ethoxyl acid amides medicines such as (being ethoxybenzamide).
The research data of preparation salicylonitrile is many, but has few that scale prodn is worth, and mainly contain: (1) salicylic aldehyde and azanol make oxime, and dehydration obtains product, US5637750, CN201010106946 then; (2) salicylic amide one step dehydration obtains product, adopts the fixed-bed catalytic high temperature dehydration, and yield 87% is fit to the above serialization scale operation of kiloton, US6248917; (3) Salicylate ammonium (perhaps Whitfield's ointment and ammonia mix) dehydration obtains product, US7629486, CN201110058467.Relative merits CN201110058467 about the whole bag of tricks introduces relatively in detail, and what need replenish here is: (1) has only salicylic amide or Salicylate ammonium dehydration preparation salicylonitrile to have clear superiority from the production cost angle; (2) from the market requirement, annual requirement is estimated about 1000 tons at present, adopts continuous production device to have high input, and the experimental verification of consistent sexual needs long reliability could really be accomplished scale production.Therefore being equipped with salicylonitrile with bigcatkin willow dehydration of amide legal system is the method that relatively is fit to large-scale production.
It is the basic skills in the organic synthesis that utilization dehydration of amide method prepares nitrile compounds, referring to the chapters and sections in " Comprehensive Organic Transformations " " Amides to Nitriles ", author Richard C.Larock.Common method has: the direct evaporations of similar powerful dehydration agent such as (1) sulfur oxychloride, POCl3, phosphorus pentachloride, phosgene, Vanadium Pentoxide in FLAKES, acid anhydrides and acyl chlorides; (2) the auxiliary dehydration of HMPA, Canadian Journal of Chemistry, 1971,49,2897; (3) Lewis acid titanium tetrachloride/triethylamine, unconventional reagent such as aluminum chloride/potassiumiodide.What wherein have industrial prospect is the first kind, considers to have vicinal hydroxyl groups in the molecule, uses Vanadium Pentoxide in FLAKES, acid anhydrides and acyl chlorides etc. to obtain other by product easily but not salicylonitrile.Sulfur oxychloride, POCl3, phosphorus pentachloride photoreactive gas in actual production process owing to its toxicity, extremely be afraid of moist and other is former thereby in actual production, be difficult to satisfy the requirement of the friendly and safe chemical process of modern environment.
The technology (Shanxi chemical industry, 2009,29,4) with TRIPHOSGENE 99.5 and salicylic amide dehydration preparation salicylonitrile has been reported in Mount Huang etc.; Salicylic amide and TRIPHOSGENE 99.5 be 100-105 ℃ of reaction in toluene, and bullion is used the toluene recrystallization, though lab scale has provided about 90% yield; But yield is not high in the actual industrial production process, and quality product is difficult to promote, and is difficult to surpass 95%; Impurity is many, influences the production of subsequent product, and what cause ICIA 5504 syntheticly is difficult to obtain high-quality product.Though though the bullion salicylonitrile repeatedly can reach 98% above content after the purifying, production cost significantly rises, and does not have practical significance.
Summary of the invention
The objective of the invention is provides a kind of method of DMF solution of eco-friendly preparation salicylonitrile in order to overcome deficiency of the prior art.
For realizing above-mentioned purpose, the present invention realizes through following technical scheme:
A kind of method of DMF solution of eco-friendly preparation salicylonitrile is characterized in that, TRIPHOSGENE 99.5 and salicylic amide is added respectively among the DMF, fully reaction.
Preferably, described salicylic amide is 1: 0.33～1.0 with the amount of substance ratio of TRIPHOSGENE 99.5.
Preferably, described salicylic amide is 1: 0.34～0.5 with the amount of substance ratio of TRIPHOSGENE 99.5.
Consider under the reaction conditions and can not strictness dewater; And in general technical grade solvent that uses and the raw material less water is arranged; It is necessary suitably improving the TRIPHOSGENE 99.5 consumption; But too much use TRIPHOSGENE 99.5 not influence the yield of salicylonitrile, comprehensive, the consumption of TRIPHOSGENE 99.5 is that the 0.34-0.5 of amount of substance of salicylic amide is both economical.
Preferably, temperature of reaction is-20～50 ℃.
Preferably, temperature of reaction is 5 ℃～15 ℃.
Temperature is too low, and energy consumption is higher, and it is more that temperature surpasses 50 ℃ of by products, influences quality product.Therefore, during actual fabrication, as long as temperature is not less than 5 ℃, is not higher than 15 ℃; Its temperature of reaction can not intervened, if exceed this TR, need be to its cooling or intensification.
Preferably, in DMF, add TRIPHOSGENE 99.5 earlier, add salicylic amide again.
Preferably, said TRIPHOSGENE 99.5 is dissolved in inert solvent earlier, is added among the DMF again.
Preferably, in DMF, add salicylic amide earlier, add TRIPHOSGENE 99.5 again.
Preferably, TRIPHOSGENE 99.5 is dissolved in to add in the lump behind the inert solvent again and is dissolved with among the DMF of salicylic amide.
Preferably, it is characterized in that described inert solvent is selected from hydro carbons, ethers, ketone or ester class inert solvent.
Preferably, said hydro carbons inert solvent is selected from alkane, aromatic hydrocarbon or its substitutive derivative.
Preferably, said ethers inert solvent is selected from aliphatic ether, aromatic hydrocarbons ether or its substitutive derivative.
Preferably, said ketone inert solvent is selected from lower aliphatic ketone or its substitutive derivative.
Preferably, said ester class inert solvent is selected from fatty ester, aromatic esters or its substitutive derivative.
Preferably, after reaction is accomplished, add the alkali neutralization, filter the DMF solution that obtains salicylonitrile.
Preferably, described alkali comprises a kind of or its mixture in mineral alkali and the organic bases.
Preferably, said mineral alkali comprises one or more in the oxide compound, oxyhydroxide, carbonate, supercarbonate of basic metal or earth alkali metal.Like ammonia, Lithium Hydroxide MonoHydrate, Quilonum Retard, sodium hydroxide, yellow soda ash, sodium hydrogencarbonate, Pottasium Hydroxide, salt of wormwood, saleratus, Natural manganese dioxide, Marinco H, magnesiumcarbonate, quicklime, calcium hydroxide, lime carbonate, Calcium hydrogen carbonate etc. or its mixture.
Preferably, said organic bases comprises one or more in triethylamine, diethylamine and the aniline.Like triethylamine, Tributylamine, diethylammonium isopropylamine, urotropine, triethylene diamine, aniline, methylphenylamine, N, accelerine etc. or its mixture.
What the present invention adopted is two kinds of methods, and first method is to add DMF to TRIPHOSGENE 99.5 earlier to form Vilsmeier reagent, adds salicylic amide then and is formed salicylonitrile by the dehydration of Vilsmeier reagent.Second method is the DMF solution that adds TRIPHOSGENE 99.5 salicylic amide, and Vilsmeier reagent can obtain same result as the catalyzer of reaction process.
The minimum amount of DMF is 6 times of amount of substance of TRIPHOSGENE 99.5, preferably, the minimum amount of DMF be TRIPHOSGENE 99.5 amount of substance 6-20 doubly.Its objective is in order to control the concentration range of salicylonitrile in DMF at 5%-40%.This is that too rare meeting reduces production efficiency because consider the needs of production application, and it is difficult that too dense meeting is stirred product separation and next step reaction, and reasonable is that the controlling concn scope is at 15%-25%.At this time DMF is in excess in theoretical consumption greatly, need not to consider the influence of DMF absorbing hydrogen chloride in the reaction process.
Second purpose of the present invention provides a kind of DMF solution of salicylonitrile, it is characterized in that, adopts aforesaid method production.
The 3rd purpose of the present invention provides a kind of salicylonitrile, it is characterized in that, adopts the DMF solution of the salicylonitrile of preceding method production, separates obtaining salicylonitrile.
The 4th purpose of the present invention provides a kind of application of DMF solution in synthetic ICIA 5504 and bunitrolol of salicylonitrile.The DMF solution of the salicylonitrile among the present invention both can directly apply to the synthetic of ICIA 5504 and Betriol (Boehringer,Ing.).Apply to the synthetic of ICIA 5504 and Betriol (Boehringer,Ing.) after also can neutralizing with alkali.
Preparing method among the present invention can obtain content greater than 98% salicylonitrile (deduction solvent), and chemical conversion rate and selectivity directly apply to next step reaction and have no problem all greater than 99%.Do not have contaminative waste gas and discharge of wastewater in process of production, the organic amine salt hydrochlorate that residue maybe can be recycled for the inorganic salt that can directly utilize has significantly reduced the comprehensive production cost of salicylonitrile, is an environmentally friendly production technique.
Embodiment
Below in conjunction with embodiment the present invention is further specified.
Embodiment 1
Under the mixture of ice and water cooling, 11.88 gram (0.04mol) TRIPHOSGENE 99.5s join among 50 milliliters of DMF in batches.Adding continued stirred 30 minutes.Controlled temperature is no more than 15 ℃.13.7 gram salicylic amide (0.1mol) joins in the above-mentioned reaction solution controlled temperature 5-15 ℃ in batches.The water cooling of reinforced completion recession deicing is bathed, and is warmed up to room temperature naturally, continues to stir one hour, obtains the DMF solution of salicylonitrile.Salicylonitrile content is 98.3%.The chemical conversion rate is 99.1%; Selectivity is 98.2%.
Embodiment 2
Under the mixture of ice and water cooling, 11.88 gram (0.04mol) TRIPHOSGENE 99.5s join among 50 milliliters of DMF in batches.Adding continued stirred 30 minutes.Controlled temperature is no more than 15 ℃.13.7 gram salicylic amide (0.1mol) joins in the above-mentioned reaction solution controlled temperature 5-15 ℃ in batches.The water cooling of reinforced completion recession deicing is bathed, and is warmed up to room temperature naturally, continues to stir one hour; Again be cooled to 15 ℃ with mixture of ice and water.Add salt of wormwood 16.56 grams (0.12mol), stir the water-bath of 15 minutes recession deicings, be warmed up to room temperature naturally and continue to stir 6 hours, filter the DMF solution that obtains salicylonitrile.Salicylonitrile content is 98.6%.The chemical conversion rate is 99.4%; Selectivity is 98.4%.
Embodiment 3
Under the mixture of ice and water cooling, 11.88 gram (0.04mol) TRIPHOSGENE 99.5s are dissolved in 25 milliliters of ETHYLE ACETATE and are added drop-wise among 50 milliliters of DMF, add continued and stir 30 minutes.Controlled temperature is no more than 15 ℃.13.7 gram salicylic amides (0.1mol) are joined in the above-mentioned reaction solution controlled temperature 5-15 ℃ in batches.The water cooling of reinforced completion recession deicing is bathed, and is warmed up to room temperature naturally, continues to stir one hour, and the steaming of Rotary Evaporators concentrating under reduced pressure removes the DMF solution that ETHYLE ACETATE obtains salicylonitrile.Salicylonitrile content is 98.7%.The chemical conversion rate is 99.5%; Selectivity is 98.5%.
Embodiment 4
Under the mixture of ice and water cooling, 11.88 gram (0.04mol) TRIPHOSGENE 99.5s are dissolved in 25 milliliters of ETHYLE ACETATE and are added drop-wise among 40 milliliters of DMF, add continued and stir 30 minutes.Controlled temperature is no more than 15 ℃.13.7 gram salicylic amide (0.1mol) is dissolved in 10 milliliters of DMF and is added drop-wise in the above-mentioned reaction solution controlled temperature 5-15 ℃.The water cooling of reinforced completion recession deicing is bathed, and is warmed up to room temperature naturally, continues to stir one hour; Again be cooled to 15 ℃ with mixture of ice and water; Add salt of wormwood 16.56 grams (0.12mol), stir the water-bath of 15 minutes recession deicings, be warmed up to room temperature naturally and continue to stir 6 hours; Filter, the Rotary Evaporators concentrating under reduced pressure steams and removes the DMF solution that ETHYLE ACETATE obtains salicylonitrile.Salicylonitrile content is 98.5%.The chemical conversion rate is 99.2%; Selectivity is 98.3%.
Embodiment 5
Under the mixture of ice and water cooling, earlier 13.7 gram salicylic amides (0.1mol) are added among 50 milliliters of DMF.Again 11.88 gram (0.04mol) TRIPHOSGENE 99.5s are added in batches, add continued and stirred 30 minutes.Controlled temperature 5-15 ℃.The water cooling of reinforced completion recession deicing is bathed, and is warmed up to room temperature naturally, continues to stir one hour, obtains the DMF solution of salicylonitrile.Salicylonitrile content is 98.2%.The chemical conversion rate is 99.1%; Selectivity is 98.3%.
Embodiment 6
Under the mixture of ice and water cooling, earlier 13.7 gram salicylic amides (0.1mol) are added among 50 milliliters of DMF, add 11.88 gram (0.04mol) TRIPHOSGENE 99.5s more in batches.Controlled temperature 5-15 ℃.The water cooling of reinforced completion recession deicing is bathed, and is warmed up to room temperature naturally, continues to stir one hour; Again be cooled to 15 ℃ with mixture of ice and water, add salt of wormwood 16.56 grams (0.12mol), stir the water-bath of 15 minutes recession deicings, be warmed up to room temperature naturally and continue to stir 6 hours, filter the DMF solution that obtains salicylonitrile.Salicylonitrile content is 98.3%.The chemical conversion rate is 99.2%; Selectivity is 98.4%.
Embodiment 7
Under the mixture of ice and water cooling; Earlier 13.7 gram salicylic amides (0.1mol) are added among 50 milliliters of DMF, again 11.88 gram (0.04mol) TRIPHOSGENE 99.5s are dissolved in 25 milliliters of ETHYLE ACETATE, be added drop-wise in the DMF solution of salicylic amide; Add continued and stirred controlled temperature 5-15 ℃ 30 minutes.The water cooling of reinforced completion recession deicing is bathed, and is warmed up to room temperature naturally, continues to stir one hour; Again be cooled to 15 ℃ with mixture of ice and water, add salt of wormwood 16.56 grams (0.12mol), stir the water-bath of 15 minutes recession deicings, be warmed up to room temperature naturally and continue to stir 6 hours, filtering and concentrating ETHYLE ACETATE obtains the DMF solution of salicylonitrile.Salicylonitrile content is 98.5%.The chemical conversion rate is 99.4%; Selectivity is 98.3%.
Application implementation example 1
In the DMF solution of the salicylonitrile that in embodiment 1, obtains; Add 32 gram (0.095mol; Content 95%, Shanghai Heben-eastsun Medicaments Co., Ltd. provides) (E)-2-[2-(6-chloropyrimide-4-base oxygen base) phenyl]-3-methoxy-methyl acrylate, 24.84 gram (0.18mol) Anhydrous potassium carbonates; Be warmed up to 50 ℃, stirred one hour; Continue to be warmed up to 100-110 ℃ then and stirred 5 hours, decompression steams DMF, and raffinate is cooled to 80 ℃, adds 50 milliliters in 100 milliliters of toluene and water; Tell the toluene phase, wash successively with 20 milliliter of 5% Hydrogen chloride and 20 milliliters of saturated sodium bicarbonates; Obtain oily matter after concentrating toluene, once obtain 36 gram ICIA 5504s, content 98.1% (external standard method), yield 92.2% with 15 ml methanol recrystallizations.
Application implementation example 2
In the DMF solution of the salicylonitrile that in embodiment 2, obtains, add 32 gram (0.095mol, content 95%; Shanghai this medicine company of standing grain provides) (E)-2-[2-(6-chloropyrimide-4-base oxygen base) phenyl]-3-methoxy-methyl acrylate, 8.28 gram (0.06mol) Anhydrous potassium carbonates are warmed up to 100-110 ℃; Stirred 5 hours; Decompression steams DMF, and raffinate is cooled to 80 ℃, adds 50 milliliters in 100 milliliters of toluene and water; Tell the toluene phase, wash successively with 20 milliliter of 5% Hydrogen chloride and 20 milliliters of saturated sodium bicarbonates; Obtain oily matter after concentrating toluene, once obtain 36.5 gram ICIA 5504s, content 98.5% (external standard method), yield 93.9% with 15 ml methanol recrystallizations.
Application implementation example 3
In embodiment 3, in the salicylonitrile DMF solution of preparation, add 9.25 gram (0.1mol) epoxy chloropropane, 30.36 gram (0.22mol) Anhydrous potassium carbonates are warmed up to 80 ℃ and stirred cool to room temperature 3 hours; Add 10.97 gram (0.15mol) TERTIARY BUTYL AMINEs, stirred 6 hours under the room temperature, remove excessive TERTIARY BUTYL AMINE and solvent DMF under reduced pressure, raffinate adds 50 milliliters of ETHYLE ACETATE and 15 ml waters; Tell organic phase; Wash at twice with 30 milliliters of saturated brines, drying concentrates and to obtain bullion 25 gram 2-[3-(1; The 1-dimethyl ethyl is amino)-2-hydroxyl propoxy-] cyanobenzene (bunitrolol); Handle with 85 milliliters of 15% hydrogenchloride/ethanolic soln again and obtain product Betriol (Boehringer,Ing.) 26.2 grams, content＞99% (HPLC), yield 91%.
Application implementation example 4
In embodiment 4, in the salicylonitrile DMF solution of preparation, add 9.25 gram (0.1mol) epoxy chloropropane, 13.8 gram (0.1mol) Anhydrous potassium carbonates are warmed up to 80 ℃ and stirred cool to room temperature 3 hours; Add 10.97 gram (0.15mol) TERTIARY BUTYL AMINEs, stirred 6 hours under the room temperature, remove excessive TERTIARY BUTYL AMINE and solvent DMF under reduced pressure, raffinate adds 50 milliliters of ETHYLE ACETATE and 15 ml waters; Tell organic phase; Wash at twice with 30 milliliters of saturated brines, drying concentrates and to obtain bullion 25.3 gram 2-[3-(1; The 1-dimethyl ethyl is amino)-2-hydroxyl propoxy-] cyanobenzene (bunitrolol); Handle with 85 milliliters of 15% hydrogenchloride/ethanolic soln again and obtain product Betriol (Boehringer,Ing.) 26.7 grams, content＞99% (HPLC), yield 92.8%.
Application implementation example 5
In the DMF solution of the salicylonitrile that in embodiment 5, obtains; Add 32 gram (0.095mol; Content 95%, Shanghai this medicine company of standing grain provides) (E)-2-[2-(6-chloropyrimide-4-base oxygen base) phenyl]-3-methoxy-methyl acrylate, 24.84 gram (0.18mol) Anhydrous potassium carbonates; Be warmed up to 50 ℃, stirred one hour; Continue to be warmed up to 100-110 ℃ then and stirred 5 hours, decompression steams DMF, and raffinate is cooled to 80 ℃, adds 50 milliliters in 100 milliliters of toluene and water; Tell the toluene phase, wash successively with 20 milliliter of 5% Hydrogen chloride and 20 milliliters of saturated sodium bicarbonates; Obtain oily matter after concentrating toluene, once obtain 35.8 gram ICIA 5504s, content 98.1% (external standard method), yield 91.7% with 15 ml methanol recrystallizations.
Application implementation example 6
In the DMF solution of the salicylonitrile that in embodiment 6, obtains, add 32 gram (0.095mol, content 95%; Shanghai this medicine company of standing grain provides) (E)-2-[2-(6-chloropyrimide-4-base oxygen base) phenyl]-3-methoxy-methyl acrylate; 8.28 gram (0.06mol) Anhydrous potassium carbonate is warmed up to 100-110 ℃ and stirred 5 hours, decompression steams DMF; Raffinate is cooled to 80 ℃, adds 50 milliliters in 100 milliliters of toluene and water; Tell the toluene phase, wash successively with 20 milliliter of 5% Hydrogen chloride and 20 milliliters of saturated sodium bicarbonates; Obtain oily matter after concentrating toluene, once obtain 36.1 gram ICIA 5504s, content 98.6% (external standard method), yield 93% with 15 ml methanol recrystallizations.
Application implementation example 7
In embodiment 7, in the salicylonitrile DMF solution of preparation, add 9.25 gram (0.1mol) epoxy chloropropane, 13.8 gram (0.22mol) Anhydrous potassium carbonates are warmed up to 80 ℃ and stirred cool to room temperature 3 hours; Add 10.97 gram (0.15mol) TERTIARY BUTYL AMINEs, stirred 6 hours under the room temperature, remove excessive TERTIARY BUTYL AMINE and solvent DMF under reduced pressure, raffinate adds 50 milliliters of ETHYLE ACETATE and 15 ml waters; Tell organic phase; Wash at twice with 30 milliliters of saturated brines, drying concentrates and to obtain bullion 25.2 gram 2-[3-(1; The 1-dimethyl ethyl is amino)-2-hydroxyl propoxy-] cyanobenzene (bunitrolol); Handle with 85 milliliters of 15% hydrogenchloride/ethanolic soln again and obtain product Betriol (Boehringer,Ing.) 26.4 grams, content＞99% (HPLC), yield 91.8%.
Embodiment among the present invention only is used for that the present invention will be described, does not constitute the restriction to the claim scope, and other substituting of being equal in fact that those skilled in that art can expect are all in protection domain of the present invention.
Claims (21)
1. the method for the DMF solution of an eco-friendly preparation salicylonitrile is characterized in that, TRIPHOSGENE 99.5 and salicylic amide is added respectively among the DMF, fully reaction.
2. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 1 is characterized in that, described salicylic amide is 1: 0.33～1.0 with the amount of substance ratio of TRIPHOSGENE 99.5.
3. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 2 is characterized in that, described salicylic amide is 1: 0.34～0.5 with the amount of substance ratio of TRIPHOSGENE 99.5.
4. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 1 is characterized in that, temperature of reaction is-20～50 ℃.
5. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 4 is characterized in that, temperature of reaction is 5～15 ℃.
6. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 1 is characterized in that, in DMF, adds TRIPHOSGENE 99.5 earlier, adds salicylic amide again.
7. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 6 is characterized in that said TRIPHOSGENE 99.5 is dissolved in inert solvent earlier, is added among the DMF again.
8. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 1 is characterized in that, in DMF, adds salicylic amide earlier, adds TRIPHOSGENE 99.5 again.
9. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 8 is characterized in that, TRIPHOSGENE 99.5 is dissolved in to add in the lump behind the inert solvent again and is dissolved with among the DMF of salicylic amide.
10. according to the method for the DMF solution of claim 7 and 9 described eco-friendly preparation salicylonitriles, it is characterized in that described inert solvent is selected from hydro carbons, ethers, ketone or ester class inert solvent.
11. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 10 is characterized in that, said hydro carbons inert solvent is selected from alkane, aromatic hydrocarbon or its substitutive derivative.
12. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 10 is characterized in that, said ethers inert solvent is selected from aliphatic ether, aromatic hydrocarbons ether or its substitutive derivative.
13. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 10 is characterized in that, said ketone inert solvent is selected from lower aliphatic ketone or its substitutive derivative.
14. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 10 is characterized in that, said ester class inert solvent is selected from fatty ester, aromatic esters or its substitutive derivative.
15. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 1 is characterized in that, after reaction is accomplished, adds the alkali neutralization, filters the DMF solution that obtains salicylonitrile.
16. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 15 is characterized in that, described alkali comprises a kind of or its mixture in mineral alkali and the organic bases.
17. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 16 is characterized in that, said mineral alkali comprises one or more in the oxide compound, oxyhydroxide, carbonate, supercarbonate of basic metal or earth alkali metal.
18. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 16 is characterized in that said organic bases comprises one or more in triethylamine, diethylamine and the aniline.
19. the DMF solution of salicylonitrile is characterized in that, adopts the described method production of the arbitrary claim of claim 1-16.
20. salicylonitrile is characterized in that, adopts the DMF solution of the salicylonitrile of the described method production of the arbitrary claim of claim 1-16, separates obtaining salicylonitrile.
21. the application of the DMF solution of salicylonitrile in synthetic ICIA 5504 and bunitrolol.
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| CN103012205A (en) * | 2012-12-26 | 2013-04-03 | 湖南海利常德农药化工有限公司 | Preparation method of salicylonitrile |
| CN103739518A (en) * | 2013-12-26 | 2014-04-23 | 安徽广信农化股份有限公司 | Synthesis process for 2-hydroxybenzonitrile |
| CN104610095A (en) * | 2015-01-04 | 2015-05-13 | 尹山红 | Preparation method of o-hydroxybenzonitrile |
| CN106496066A (en) * | 2016-09-27 | 2017-03-15 | 江苏嘉隆化工有限公司 | A kind of preparation method of salicylonitrile |
| CN109721548A (en) * | 2017-10-31 | 2019-05-07 | 南通泰禾化工股份有限公司 | A kind of preparation method of Fluoxastrobin |
| CN112094238A (en) * | 2020-09-23 | 2020-12-18 | 江苏大学 | Method for post-treatment of azoxystrobin production |
| CN114685377A (en) * | 2020-12-31 | 2022-07-01 | 北京颖泰嘉和生物科技股份有限公司 | Preparation method of azoxystrobin compound |
| CN114685376A (en) * | 2020-12-28 | 2022-07-01 | 北京颖泰嘉和生物科技股份有限公司 | Preparation method of azoxystrobin intermediate |
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| CN103739518B (en) * | 2013-12-26 | 2016-03-30 | 安徽广信农化股份有限公司 | A kind of synthesis technique of salicylonitrile |
| CN104610095A (en) * | 2015-01-04 | 2015-05-13 | 尹山红 | Preparation method of o-hydroxybenzonitrile |
| CN106496066A (en) * | 2016-09-27 | 2017-03-15 | 江苏嘉隆化工有限公司 | A kind of preparation method of salicylonitrile |
| CN109721548A (en) * | 2017-10-31 | 2019-05-07 | 南通泰禾化工股份有限公司 | A kind of preparation method of Fluoxastrobin |
| CN109721548B (en) * | 2017-10-31 | 2020-11-13 | 南通泰禾化工股份有限公司 | Preparation method of azoxystrobin |
| CN112094238A (en) * | 2020-09-23 | 2020-12-18 | 江苏大学 | Method for post-treatment of azoxystrobin production |
| CN114685376A (en) * | 2020-12-28 | 2022-07-01 | 北京颖泰嘉和生物科技股份有限公司 | Preparation method of azoxystrobin intermediate |
| CN114685377A (en) * | 2020-12-31 | 2022-07-01 | 北京颖泰嘉和生物科技股份有限公司 | Preparation method of azoxystrobin compound |
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| CN102516122B (en) | 2014-11-05 |
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